CBRNE - Smallpox Medication

Updated: Dec 16, 2014
  • Author: Christopher J Hogan, MD; Chief Editor: Duane C Caneva, MD, MSc  more...
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Medication Summary

Once smallpox is fully manifested, medical treatment consist of supportive care. Vaccinations and postexposure interventions are the mainstays of treatment.

The various vaccines available and being tested are divided into generations based on their method of manufacturing and degree of virus attenuation. First-generation vaccines are composed of vaccinia virus derived from calf lymph or chicken embryos, have little attenuation, and represent the majority of the vaccine stockpile.

Second-generation vaccines are viruses taken from first-generation vaccines that are then sterilely tissue-cultured with the aim of decreasing adverse outcomes. Lastly, third-generation vaccines use replication-deficient viruses that are highly attenuated, again with the aim of decreasing side effects and adverse outcomes.



Class Summary

The vaccinia (smallpox) vaccine and vaccinia immune globulin (VIG) are available only through the CDC and state and federal health agencies. Dryvax, and now ACAM200, are the only vaccines available, although vaccines from other countries may be made available in a smallpox outbreak. [7] One hundred million doses of the Wyeth Laboratory vaccine (New York Board of Health virus grown on scarified calves) exist in the United States. This stock was diluted in 2002, and the current stock is approximately 1000 million doses. [8] Fifty to one-hundred million additional doses are estimated to exist worldwide. Almost 750,000 doses of this vaccine have been used to vaccinate the US military. When the vaccine was made available to first-line health care individuals, 38,000 received the vaccine.

One large-scale producer of a cell-cultured smallpox vaccine (Acambis) received US Food and Drug Administration (FDA) approval on August 31, 2007, for active immunization for those determined to be at high risk for smallpox infection. It is a single-dose vaccine that is the primary smallpox vaccine for use in the Strategic National Stockpile, with 192.5 million doses produced. Although believed to have less potential for adverse outcomes, ACAM2000 has been found to have similar rates of side effects such as myopericarditis.

Also under development is a modified vaccinia virus Ankara (MVA), which may be suitable as a new smallpox vaccine. Because it uses an attenuated virus, it can theoretically be used in those with contraindications to a first- or second-generation vaccine. When given prior to administration of Dryvax, it was shown to increase the immune response to vaccination while decreasing the severity of the lesion formation. [9] Although this attenuated strain was used in Europe in the 1960s, it has never been field tested against an actual smallpox epidemic, unlike the first-generation vaccines (thus, its effectiveness in protecting against infection was never evaluated).

Persons exposed to variola (meaning all household or other face-to-face contacts after onset of fever) within a few days were found to experience attenuated illness if vaccinated within 4 days. Researchers estimate that, of the previously vaccinated population, only approximately 20% still have effective immunity. Those who were not revaccinated within 3 years (eg, laboratory workers) should be vaccinated again. [8] From the most recent military vaccination campaign, postvaccinial encephalitis or encephalomyelitis has been reported to occur at an incidence of 1 case per 300,000 vaccinations, and myopericarditis has been found in a significantly higher number of patients. [10, 8, 11, 12]

Vaccinia virus vaccine (ACAM2000)

Made from vaccinia, which is related to but different from the virus that causes smallpox. ACAM2000 (Sanofi Pasteur Biologics) was approved by the FDA for active immunization against smallpox disease for persons determined to be at high risk for smallpox infection on August 31, 2007.

Contains live vaccinia virus and works by causing a mild infection that stimulates an immune response that effectively protects against smallpox without actually causing disease. Vaccine contains live vaccinia virus but does not contain variola virus, the virus that causes smallpox. Vaccinia is a member of the orthopoxvirus genus, which includes smallpox (variola), cowpox, monkeypox, gerbilpox, camelpox, and others. Following inoculation, vaccine induces an immune reaction that serves to protect against smallpox.

Derived from the only other smallpox vaccine licensed by the FDA (Dryvax), which was approved in 1931 and is now in limited supply because it is no longer manufactured. US military resumed vaccination of at-risk personnel in 1999 after concluding the disease posed a potential bioterrorism threat. A recent meta-analysis suggests that stockpiled vaccines have maintained their immunogenicity and that the newer cell-cultured vaccines are similar to stockpiled vaccines in terms of vaccination success rate and immunogenicity.

ACAM2000 was studied in 2 populations: (1) persons who had never been vaccinated for smallpox and (2) those who had received smallpox vaccination many years earlier. The percentage of unvaccinated persons who developed a successful immunization reaction was similar to that of Dryvax. ACAM2000 was also found to be acceptable as a booster in persons previously vaccinated for smallpox. The female gender has been found to have a better immune response to immunization.

Because ACAM2000 contains live vaccinia virus, care must be taken to prevent virus from spreading from inoculation site to other parts of the body and to other individuals.

To minimize known risks, vaccine licensing is subject to a Risk Minimization Action Plan (RiskMAP), which requires providers of the vaccine and patients to be educated about these and other risks.

The medication guide explains proper care of the vaccination site and provides information about serious adverse effects associated with ACAM2000. In studies, about 1 in 175 healthy adults who received smallpox vaccine for the first time developed myocarditis and/or pericarditis. Of the 10 affected adults, 4 had no symptoms at the end of the study and symptoms resolved in all but one.

Manufactured by Acambis Inc of Cambridge, England, and Cambridge, Mass. Dryvax was made by Wyeth Laboratories Inc based in Madison, NJ.

Imvamune is a modified vaccinia Ankara strain that has recently completed Phase I trials with promising results. It may be an alternative to high-risk populations (people diagnosed with atopic dermatitis or infected with HIV) due to its low adverse event profile.


Blood products

Class Summary

Immune globulins bind to the virus particle, stimulate an immune response, and offer transient protection while the host immune system develops antibodies. A new VIG is being developed. The IV route is anticipated to be the preferred method of administration, and new dosage recommendations (eg, lower dose than the current IM product) are expected. The new VIG contains low-aggregated protein levels, allowing IV or IM administration.

Immune globulin (IVIG; Gammagard S/D, Gammar-P, Gamunex, Polygam S/D)

Can be administered within 3 d of exposure but is best if given within 24 h; may be necessary to administer VIG in adverse reactions to vaccination; because production of VIG ceased in 1970s, its efficacy (because of its age) is under question; in possession of the CDC


Immune globulins

Class Summary

Indicated for passive immunity. VIG is the only drug available for amelioration of some vaccinia-related complications. VIG is produced from pooled human sera taken from vaccinia-immunized individuals and is available only from the CDC. VIG has been effective when administered early in cases of vaccinia necrosum and eczema vaccinatum. VIG has not been effective in cases of encephalopathy. The use of VIG for generalized vaccinia reactions is usually not necessary. Recently, VIGIV has been FDA approved.

Vaccinia immune globulin intravenous, human (VIGIV)

Derived from human plasma and manufactured from pooled plasma donors who received booster immunizations with smallpox vaccine (Dryvax). Contains increased antibody levels against vaccinia virus. Indicated to treat rare adverse reactions and aberrant infections caused by vaccinia virus, including aberrant infections (eg, accidental implantation in eyes, mouth, other potentially hazardous areas), eczema vaccinatum, progressive vaccinia, severe generalized vaccinia, and vaccinia infections in immunocompromised individuals.



Class Summary

In vitro studies demonstrated cidofovir to inhibit poxvirus replication and cell lysis.

Cidofovir (Vistide)

In vitro studies demonstrated cidofovir to inhibit poxvirus replication and cell lysis. New research demonstrates that chemical inhibitors of host-signaling pathways exploited by viral pathogens may represent potent antiviral therapies.

This drug must be used under an FDA Investigational New Drug (IND) protocol because it is not licensed for use as a treatment of smallpox. Cidofovir is a nucleoside analog DNA polymerase inhibitor; if administered within 48 h of exposure, may attenuate or avoid infection; adefovir, cidofovir, and ribavirin are under investigation for use in smallpox. Ribavirin as an aerosol treatment for pediatric respiratory syncytial virus is under investigation.